tbuckley/cabot-search huggingface dataset:
Results of an online, globally-available survey to determine modes of cancer treatment education used by patients with cancer.
Authors: Jeffrey A Gilreath, Daphne D Goewey, Mimi Lo, Colleen McCabe, Anthony Greenly, Brandon Wilds, David D. Stenehjem
Journal: Journal of Clinical Oncology (2022)

e18523 Background: Many patients with cancer (PwC) possess a suboptimal understanding of their chemotherapy treatment plan. 1 Accordingly, PwC may seek information regarding both the disease and its treatment from other resources. Purpose: A freely-accessible website was curated by oncology pharmacists to provide evidence-based educational material on chemotherapy treatment plans. Objective: To use the website to deploy an online survey assessing other modes of education routinely accessed by PwC. Methods: Between February 2020 and January 2021, PwC completed an anonymous, English language survey via www.chemoexperts.com. Results: A total of 1,036 self-identified patient users began the survey. The majority were from North America (75%). Most respondents (65%) were female. PwC were asked: “If you received education from a health care professional (HCP), what type of education did you receive?” Multiple responses were allowed. Of the 820 patients who responded to this question, 77.4% (n = 635) were given printed material, 52.3% (n = 429) were taught in clinic, 8% (n = 66) were shown videos, 5.7% (n = 47) participated in an educational class outside of clinic, and 4% (n = 33) were given magazines. Roughly 37% were directed to an internet site (n = 304; 92 to chemoexperts.com, 212 to other internet sites) by a HCP. Patients also reported using blogs (12.7%; n = 111/873 respondents), websites other than chemoexperts (85%; n = 742/873), support groups (28.4%; n = 248/873), and YouTube (15.1%; n = 132/873). Discussion: In-person teaching sessions are vital to understanding treatment plans. While the ongoing COVID-19 pandemic may have lowered the percentage of PwC who are offered teaching, some PwC may still not absorb or retain all there is to know during in-person sessions and seek other resources to bolster their understanding of treatment. Although the majority of users reported receiving printed material, this too may be limited in its ability to meet the needs of all individuals. Knowing PwC may seek varying modes of education, HCPs should direct patients to resources they are familiar with. Conclusions: To our knowledge, this is the first global survey to examine modes of education utilized by PwC. Although PwC may receive teaching in person, many still seek a variety of educational resources outside of clinic. Relying solely on printed material will not meet the needs of some PwC. When educating PwC in clinic, HCPs concerned about the validity of outside materials should direct patients to resources they are familiar with and trust. Reference: Almalki H, Absi A, Alghamdi A, Alsalmi M, Khan M. Analysis of Patient-Physician Concordance in the Understanding of Chemotherapy Treatment Plans Among Patients With Cancer. JAMA Netw Open. 2020 Mar 2;3(3):e200341.
A multiple center, open-label, single-arm, phase II clinical trial of MRG002, an HER2-targeted antibody-drug conjugate, in patients with HER2-low expressing advanced or metastatic breast cancer.
Authors: Zefei Jiang, Tao Sun, Xiaojia Wang, Qiang Liu, Min Yan, Zhongsheng Tong, Cuizhi Geng, Jinhai Tang, Yongmei Yin, Guohua Yu, Jingfen Wang, Wuyun Su, Shusen Wang, Yueyin Pan, Hua Yang
Journal: Journal of Clinical Oncology (2022)

1102 Background: MRG002 is a novel HER2-targeted ADC, composed of a sugar-modified trastuzumab, MMAE payload and a cleavable vc-linker. MRG002 was effective in HER2-low expressing breast cancer in preclinical studies. Hence, we conducted the phase II study to evaluate the safety and anti-tumor efficacy of MRG002 in HER-low breast cancer. Methods: HER2 low tumor expression was determined by a central lab and had to be immunohistochemistry (IHC)1+ or 2+/ISH-. Eligible patients had advanced/metastatic HER2-low expressing breast cancer that failed standard therapies. MRG002 was administered intravenously once every 3 weeks at the dose of 2.6 mg/kg, until disease progression or unacceptable toxicity which ever occurred first. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC). The secondary endpoints were progression-free survival (PFS), disease control rate (DCR), and safety. Results: A total of 56 female patients with HER2-low advanced or metastatic breast cancer were enrolled at the time of data cut-off (Dec 31, 2021) and had received at least one cycle of MRG002. The median age was 55 (30-72) years. Most patients were HER2 IHC1+ (83.9%), hormone receptor positive (HR+) (85.7%), and with a ECOG PS of 1 (57.1%). Twenty-eight patients (50.0%) had received at least 2 lines of chemotherapy and the median treatment was 3. Forty-one patients (73.2%) had visceral metastasis and 31 patients (55.4%) had bone metastasis. The ORR and DCR in 49 evaluable patients were 34.7% and 75.5%, with 17 PR, 20 SD and 12 PD. Subgroup analysis indicated that the ORR was 39.5% (15/38) and DCR was 76.3% (29/38) among the evaluable patients with visceral metastasis. The tumor responses were similar in both the HER2 IHC 1+ and IHC 2+ subgroups, as is 34.1% and 37.5% respectively, which might be attributed to fewer IHC 2+ enrollment in this trial. Although only 8 HR- subjects enrolled in our study, the ORR (37.5%) and DCR (62.5%) is promising in these triple negative BC patients post to ≥2 line therapies. Most common treatment related adverse events (TRAEs) were grade 1 or 2. The most common TRAEs (≥20%) were neutrophil count decreased (53.6%), white blood cell count decreased (48.2%), AST increased (46.4%), alopecia and ALT increased (39.3%), blood lactate dehydrogenase increased(33.9%), GGT increased (32.1%), nausea (32.1%), vomiting (23.2%), constipation (23.2%), diarrhea(23.2%) and hyperglycemia (21.4%). Most common grade ≥3 TRAE(≥10%) was neutrophil count decreased(14.3%). No patients died due to MRG002. Conclusions: MRG002 shows promising efficacyand well tolerated in patients with HER2-low breast cancer. Further evaluation is underway. Clinical trial information: NCT04742153.
Real-world outcomes of neoadjuvant chemotherapy for breast cancer: Reflections from a community cancer center.
Authors: Prarthna V Bhardwaj, Seth Kaufman, Holly Mason, Paul Visintainer, Grace Makari-Judson
Journal: Journal of Clinical Oncology (2022)

e18690 Background: Neoadjuvant chemotherapy (NAC) has been historically reserved for patients with locally advanced breast cancers. The utilization of NAC remains highly variable in clinical practice based on tumor size and receptor status. The decision to pursue NAC is often based on discussions by a multidisciplinary team (MDT). This study aims to look at real-world data describing the contemporary use of NAC in patients with early-stage operable breast cancer in a community cancer center and evaluate the effectiveness of MDT at our institution. Methods: We conducted a retrospective descriptive study at UMass Chan-Baystate between Oct 2018 and Oct 2020. We included patients receiving NAC for early-stage operable or locally advanced breast cancer. We excluded patients receiving neoadjuvant endocrine therapy. Primary outcomes were rates of pathological complete response (pCR) after surgery. Secondary outcomes were referral timeliness back to the breast surgeon and radiation oncologist, downstaging of cancer in the breast and axilla. Results: Ninety-three patients underwent NAC, of which 84% were white. The mean age was 56.6 yrs. Of these, 86 (93%) had clinical stage II or III cancer, and 80 (86%) had positive lymph nodes. Forty-two patients (46%) were ER positive, 28 (30%) were HER2 positive and 39 (43%) were triple negative. The most common indication for NAC was to downstage axilla (42%) and for HER2 tailoring of treatment (26%). Of the 93 patients, 23 (25%) achieved pCR; 12 (52%) had triple-negative, 7 (30%) had ER-HER2+, 3 (13%) had ER+HER2+ and 1 (4%) had ER+HER2- breast cancer. Eighty-four patients (91%) had downstaging of breast tumor, and 30 (32.3%) had axillary downstaging. Seventy-eight patients (84%) received adjuvant radiation (RT). All patients (N = 93, 100%) followed up with a surgeon prior to completion of NAC, although only 48 (50%) returned to radiation oncology. The mean time from surgery to RT was 64 days, and 6% underwent RT for more than two weeks beyond the expected time. Conclusions: Overall pCR rates were low; however, a third of patients had axillary downstaging, and the majority had breast tumor downstaging. Of the patients in our cohort who achieved pCR, the majority were triple-negative, followed by HER2 positive, consistent with overall trends. All patients were re-referred to the surgeon prior to completion of NAC for surgical planning and the average time from surgery to radiation was within national standards highlighting effective MDT involvement in the care of patients at our institution.[Table: see text]
The PIONEER watchful waiting for prostate cancer apps - a first practical application of using big data for prostate cancer
Authors: T. Hulsen, M. Moinat, K. Van Bochove, A. Gorbachev, D. Kaduk, G. Argyriou, S. Cossin, R. Herrera, A. Golozar, P. Prinsen, K. Beyer, M. Van Hemelrijck, M. Oja, S. Axelsson, C. Steinbeisser, B. De Meulder
Journal: European Urology (2022)
Lymphocyte crosstalk is required for monocyte-intrinsic trained immunity to Plasmodium falciparum
Authors: Juliet N. Crabtree, Daniel R. Caffrey, Leandro de Souza Silva, Evelyn A. Kurt-Jones, Katherine Dobbs, Arlene Dent, Katherine A. Fitzgerald, Douglas T. Golenbock
Journal: Journal of Clinical Investigation (2022)

Plasmodium falciparum (P. falciparum) induces trained innate immune responses in vitro, where initial stimulation of adherent PBMCs with P. falciparum–infected RBCs (iRBCs) results in hyperresponsiveness to subsequent ligation of TLR2. This response correlates with the presence of T and B lymphocytes in adherent PBMCs, suggesting that innate immune training is partially due to adaptive immunity. We found that T cell–depleted PBMCs and purified monocytes alone did not elicit hyperproduction of IL-6 and TNF-α under training conditions. Analysis of P. falciparum–trained PBMCs showed that DCs did not develop under control conditions, and IL-6 and TNF-α were primarily produced by monocytes and DCs. Transwell experiments isolating purified monocytes from either PBMCs or purified CD4+ T cells, but allowing diffusion of secreted proteins, enabled monocytes trained with iRBCs to hyperproduce IL-6 and TNF-α after TLR restimulation. Purified monocytes stimulated with IFN-γ hyperproduced IL-6 and TNF-α, whereas blockade of IFN-γ in P. falciparum–trained PBMCs inhibited trained responses. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq) on monocytes from patients with malaria showed persistently open chromatin at genes that appeared to be trained in vitro. Together, these findings indicate that the trained immune response of monocytes to P. falciparum is not completely cell intrinsic but depends on soluble signals from lymphocytes.
OTHR-31. The molecular profile of secondary meningiomas in survivors of childhood non-central nervous system (CNS) cancers
Authors: Catherine Corriveau-Bourque, Derek Wong, Frank van Landeghem, Matija Snuderl, Maria Spavor, Stephen Yip, David Eisenstat
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Secondary meningiomas are a late effect in children who received cranial irradiation, frequently with a long latency. The molecular genetic profile of primary meningiomas is well studied; however, few studies describe the genomic landscape of radiation-induced meningiomas (RIM). METHODS: Patients followed at the Stollery Children’s Hospital (Edmonton, Canada) with a history of non-CNS malignancies who received cranial irradiation and then developed meningiomas between 1971 and 2013 were identified. Whole exome sequencing (WES), RNA sequencing as well as DNA methylation profiling were performed for patients with available tumor tissue and germline DNA. RESULTS: Of 96 patients who received cranial irradiation for non-CNS tumors, 16 (16.7%) developed symptomatic meningiomas. This patient cohort is unique; all 16 patients identified received 2000-2400 cGy of cranial irradiation, suggesting a threshold dose. 9/16 (56%) had WHO Grade 2 meningiomas or greater and 7/16 (44%) of meningiomas infiltrated other tissues. Post-surgical recurrences occurred in 43%. Patients experienced considerable morbidities directly attributable to the meningiomas or their treatment. 14 patients had samples suitable for further analysis. NF2 mutations were identified in 50% (8; 4 DNA,4 fusion). Other meningioma related genes with mutations identified in other cohorts were not identified. Copy number alternations were noted in all 16 patients in chromosomes 1p and 22q. 850k methylation analysis with PCA as well as UMAP and tSNE did not demonstrate clustering. Ongoing additional studies include examining tumor mutation burden and the radiation mutational profile. CONCLUSIONS: This study examined the RIM in a cohort of patients having received similar doses of radiation for their childhood cancer. There is increased risk of radiation-induced meningioma in survivors of non-CNS cancers given ≥ 2000 cGy during childhood. To date, our findings are consistent with previously described primary and RIM mutations. Enhanced knowledge in secondary meningiomas is crucial for accurate patient counselling, prognostication, and treatment.
RARE-12. Pineoblastoma of children and young adults in a national population: An analysis of the HIT-MED study cohort
Authors: Mathias Yuan, Martin Mynarek, Tobias Goschzik, Elke Pfaff, Rolf Kortmann, Brigitte Bison, Monika Warmuth-Metz, Ulrich Schiller, Christian Hagel, Denise Obrecht, Martin Benesch, Stefan M Pfister, Torsten Pietsch, Stefan Rutkowski
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Pineoblastoma is a malignant tumor of the pineal gland and accounts for &amp;lt;1% of all pediatric brain tumors. PURPOSE/METHODS: Patients &amp;lt;21 years (y) with pineoblastoma confirmed by central neuropathology review between 2001–2021 and included into the HIT2000 trial, HIT2000interim- or I-HIT-MED-registries were eligible. RESULTS: 88 patients were identified. Age at diagnosis was 0.01–20.71y (median 9.34y), median follow-up was 6.54y (IQR 1.78–12.41y) in 48 patients alive at last follow-up. 20 patients were &amp;lt;4y and received chemotherapy with intent to avoid radiotherapy. Of these, 7 patients were alive at last follow-up, two patients were radiotherapy-naïve and 5 patients had undergone CSI + boost (4 after incomplete response and one after progression). 5-y-PFS/OS in 68 patients &amp;gt;4y differed according to metastatic status (M0 (n=40) 72.7±8.3%/75.0±8.3%; M+ (n=28) 28.7±10.3%/40.8±10.9%, p=0.001/0.001). Therapy escalation in M0 patients by giving SKK chemotherapy before radiotherapy did not improve PFS/OS compared to upfront radiotherapy (5-y-PFS/OS 70.7±14.3%/70.0±14.5% vs 74.2±10.1%/78.9±9.4%, p=0.61/0.73). Applied CSI dosages were 24–50Gy (mean 35.6Gy) with no prognostic value of specific dosages being observed. Similarly, in M0 patients hyperfractionated radiotherapy (2x1.0Gy/d, total dose (TD) 36Gy, n=23) was not superior to conventional radiotherapy (1.6Gy/d, TD 35.2Gy, n=7). In all patients, favorable prognostic factors were age &amp;gt;4y (5-y-PFS/OS 54.1±7.0%/60.0±7.0% vs 30.0 ±10.2%/35.0±10.7%, p=0.012/0.053) and radiotherapy in primary therapy (5-y-PFS/OS 55.8±6.5%/61.4±6.4% vs 14.4±9.4%/21.4±11.0%, p&amp;lt;0.001/=0.003), whereas unfavorable prognosis was associated with metastatic disease (5-y-PFS/OS 33.6±9.0%/45.9±9.3% vs 58.8±7.6%/59.3±7.7%, p=0.028/0.086). CONCLUSION: Survival is poor in pineoblastoma patients &amp;lt;4y treated without radiotherapy. Unfavorable prognosis was associated with metastatic disease, especially in older children. Chemotherapy combined with CSI is effective for non-metastatic patients at age &amp;gt;4y. Further research will consider biological subgroups to enhance risk stratification and identify approaches for therapy improvements.
Expression of CD47 and CALR in myeloproliferative neoplasms: Potential new therapeutical targets.
Authors: Ciro Roberto Rinaldi, Kristian Boasman, Matthew Simmonds
Journal: Journal of Clinical Oncology (2022)

e19075 Background: Myeloproliferative neoplasms (MPN) are myeloid malignancies characterized by overproduction of mature blood cells, hyperplastic bone marrow and tendency to evolve into acute myeloid leukaemia. In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti-phagocytic CD47, reflecting an apoptosis vs survival mechanism. Increases of both CALR and CD47 on the cell membrane have been observed in response to chemotherapy, however their role in myeloid malignancies is poorly understood. Methods: Investigate the expression and cellular localisation of CALR and CD47 in untreated and treated patients with essential thrombocythemia (ET), polycythemia vera (PV) myelofibrosis (MF), in comparison with healthy controls. Mononuclear cells were collected by Ficoll separation, from peripheral blood of 30 MPN (8 PV, 16 ET, 6 MF); 18 MPN patients received cyto-reductive therapies (Hydroxyurea, Anagrelide or Ruxolitinib); and 4 controls. Cells were fractionised into 4 compartments: membrane, cytoplasm, cytosol and nucleus. Proteins were extracted using TRIzol, with CALR and CD47 protein expression analysed by western blotting. Results: Total CALR and CD47 protein expression increased in MPN samples compared with controls (CALR- 7.9 vs 5.1; CD47- 2.7 vs 2.2 fold, respectively). CD47 showed higher expression of its overall protein on MPN cell membranes when compared with CALR (22% vs 13.9%). We observed a significant reduction of CALR expression in all MPN subtypes when patients were treated with cyto-reductive agents (ET- untreated 43.3% vs treated 2%, PV- 3.6% vs 2.2%, ET- 21% vs 11%). Interestingly we have observed a significant increase in CD47 cell membrane expression after treatment in MF and PV (CD47 in MF- untreated 11.8% vs treated 34.3%, PV-11.4% vs 35.9%), suggesting an anti-phagocytic effect induced by cytotoxic drugs. In ET cell membranes however, CD47 expression is reduced after cyto-reductive treatment (22% vs 16.6%), suggesting instead a prophagocytic effect. Conclusions: CD47, but not CALR, is overexpressed on the membrane of patients with MPN, suggesting a role for CD47 as a strong antiphagocytic signal responsible for immune survival in MPN. We observed a significant difference in CD47 expression across different MPN subtypes with a significant increase in CD47 expression in PV and MF but not ET. The use of anti-CD47 antibodies could represent a new strategy to enhance the treatment response in particular in PV and MF.
Boundary-rendering network for breast lesion segmentation in ultrasound images
Authors: Ruobing Huang, Mingrong Lin, Haoran Dou, Zehui Lin, Qilong Ying, Xiaohong Jia, Wenwen Xu, Zihan Mei, Xin Yang, Yijie Dong, Jianqiao Zhou, Dong Ni
Journal: Medical Image Analysis (2022)
Phase 1 trial of ruxolitinib, temozolomide, and radiation in high-grade gliomas.
Authors: Manmeet Singh Ahluwalia, Yasmeen Rauf, Glen Stevens, David M. Peereboom
Journal: Journal of Clinical Oncology (2022)

2061 Background: Ruxolitinib is a novel, selective inhibitor of JAK1 (Janus kinase 1) and JAK2 and JAK3. JAK signaling involves recruitment of signal transducers and activators of transcription (STATs) to cytokine receptors, activation, and subsequent localization of STATs to the nucleus leading to modulation of gene expression. Dysregulation of the JAK/STAT pathway has been associated with several types of cancer and increased proliferation and survival of malignant cells. Preclinical evidence supports inhibition of JAJK STAT pathway arrogated glioma growth. Methods: Ruxolitinib is a novel, selective inhibitor of JAK1 (Janus kinase 1) and JAK2 and JAK3. JAK signaling involves recruitment of signal transducers and activators of transcription (STATs) to cytokine receptors, activation, and subsequent localization of STATs to the nucleus leading to modulation of gene expression. Dysregulation of the JAK/STAT pathway has been associated with several types of cancer and increased proliferation and survival of malignant cells. Preclinical evidence supports inhibition of JAJK STAT pathway arrogated glioma growth. Results: 60 patients were treated on the study and there were no dose limiting toxicity seen on the protocol. Survival data was calculated for GBM. The OS for arm 1 was 18.17 (10.15, NA) and was not reached for arm 2. The 1 year OS was 0.62 for arm 1 and 0.93 for arm 2. Patients that received ruxolitinib + radiation x 60 Gy + daily temozolomide at 75 mg/m2 for 6 weeks over 6 weeks (Arm 2) had significantly better PFS and OS than those that received ruxolitinib + radiation x 60 Gy alone. Conclusions: Dose of 20 mg twice daily of ruxolitinib is safe with radiation and temozolomide. Preliminary survival data appears promising compared to the historical benchmarks and randomized phase 2 trial is planned. Clinical trial information: NCT03514069. [Table: see text]
HGG-21. Oncogenic tyrosine kinase gene fusions in infant-type hemispheric gliomas - comparison of RNA- and DNA-based methods for their reliable detection
Authors: Torsten Pietsch, Gerrit Gielen, Andreas Waha, Evelyn Doerner, Andre O von Bueren, Christian Vokuhl, Glen Kristiansen, Christof Kramm
Journal: Neuro-Oncology (2022)

Abstract High-grade diffuse gliomas (HGG) in early childhood are characterized by a more favorable outcome compared to older children. We demonstrated in previous studies that these tumors have stable genomes. Activating tyrosine kinase gene fusions in infant-type hemispheric gliomas represent therapeutic targets. 50 supratentorial HGG occurring in children younger than four years were retrieved from the archives of the Brain Tumor Reference Center, Institute of Neuropathology, Bonn University. DNA and RNA were extracted from FFPE tumor samples. Gene fusions were identified on the DNA level by FISH using break-apart probes for ALK, NTRK1, -2, -3, ROS1 and MET and Molecular Inversion Probe (MIP) methodology. On the RNA level, fusion transcripts were detected by targeted RNA sequencing as well as Nanostring assay with fusion-specific probes. 37 supratentorial HGG occurred in the first year of life, 13 HGG between one and four years. 18 cases showed fusions of ALK to different partners; all occurred in the first year of life (18/37, 48.6%). Fusions of ROS1 were found in 5, MET in 3, NTRK1, -2, -3 in 10 cases. 12 cases showed no and two cases novel fusions. The different methods led to comparable results. Only recurrent fusions with known fusion partners were detectable with fusion sequence-specific Nanostring probes and library construction for targeted RNA sequencing failed in a fraction of cases. Break-apart FISH led to reliable results on the next day, and MIP technology represented the most sensitive method for analysis of FFPE samples. Gene fusions involving the tyrosine kinase genes ALK, MET, ROS1 and NTRK1, -2, -3 occurred in 72% of HGG of young children; most frequent were ALK fusions occurring in tumors of infants. DNA-based MIP technology represented the most robust and sensitive assay. A combination of RNA- and DNA-based methods to detect these fusions with high reliability is recommended.